Recent data have shown that there is a "factor" extractable from human urine which stimulates NH4 ion excretion in the toad bladder when the subject is in an NH4Cl induced acidosis. Extracts of urine from six human subjects collected during NH4Cl-induced acidosis were prepared. These extracts were tested for their effect on NH4 ion excretion in hemibladders mounted between plastic chambers. The extracts significantly increased NH4 ion excretion in the toad urinary bladder. This ammoniuretic activity was not present in the urine when the same individuals were in metabolic alkalosis. In addition, using the same techniques we are investigating the possibility that the dog also has this factor present during acidosis. We have found that both metabolic and respiratory acidotic plasma preparations from the dog caused increased ammonia excretion by the toad urinary bladder. Metabolic alkalotic plasma preparations from a dog did not produce significant ammoniuretic activity. We are also investigating the possibility that the catecholamines mediate H ion and NH4 ion excretion in the total urinary bladder. We have found that both epinephrine and norepinephrine stimulates H ion and NH4 ion excretion in toad bladder and that this response mediated via the beta receptor mechanism.